Progress in Bioprinting of Vascular Networks

Perhaps the greatest challenge in tissue engineering, and this has been true for a decade now, is creating the necessary networks of blood vessels to support large sections of tissue. The approaches to the problem are no big secret: either print the blood vessels into the tissue structure as it is assembled, or somehow guide cells into doing that job for you. Unfortunately both paths have proven to be far more difficult than anticipated, which is one of the reasons why decellularization of donor organs has received so much attention. In that case, natural vascular network structures already exist and will be recreated much as they were when the decellularized tissue is repopulated with cells cultured from a patient sample. Still, progress towards the goal of fully vascularized engineered tissue continues, either via bioprinting or carefully steered growth, with technology demonstrations such as the one noted here emerging of late:

New research addresses one of the biggest challenges in tissue engineering: creating lifelike tissues and organs with functioning vasculature - networks of blood vessels that can transport blood, nutrients, waste and other biological materials - and do so safely when implanted inside the body. Researchers from other labs have used different 3D printing technologies to create artificial blood vessels. But existing technologies are slow, costly and mainly produce simple structures, such as a single blood vessel - a tube, basically. These blood vessels also are not capable of integrating with the body's own vascular system. "Almost all tissues and organs need blood vessels to survive and work properly. This is a big bottleneck in making organ transplants, which are in high demand but in short supply. 3D bioprinting organs can help bridge this gap, and our lab has taken a big step toward that goal."

The researchers have 3D printed a vasculature network that can safely integrate with the body's own network to circulate blood. These blood vessels branch out into many series of smaller vessels, similar to the blood vessel structures found in the body. The team developed an innovative bioprinting technology, using their own homemade 3D printers, to rapidly produce intricate 3D microstructures that mimic the sophisticated designs and functions of biological tissues. Researchers first create a 3D model of the biological structure on a computer. The computer then transfers 2D snapshots of the model to millions of microscopic-sized mirrors, which are each digitally controlled to project patterns of UV light in the form of these snapshots. The UV patterns are shined onto a solution containing live cells and light-sensitive polymers that solidify upon exposure to UV light. The structure is rapidly printed one layer at a time, in a continuous fashion, creating a 3D solid polymer scaffold encapsulating live cells that will grow and become biological tissue.

"We can directly print detailed microvasculature structures in extremely high resolution. Other 3D printing technologies produce the equivalent of 'pixelated' structures in comparison and usually require sacrificial materials and additional steps to create the vessels." And this entire process takes just a few seconds - a vast improvement over competing bioprinting methods, which normally take hours just to print simple structures. The process also uses materials that are inexpensive and biocompatible. Using their technology, the team printed a structure containing endothelial cells, which are cells that form the inner lining of blood vessels. Researchers cultured several structures in vitro for one day, then grafted the resulting tissues into skin wounds of mice. After two weeks, the researchers examined the implants and found that they had successfully grown into and merged with the host blood vessel network, allowing blood to circulate normally. The implanted blood vessels are not yet capable of other functions, such as transporting nutrients and waste. "We still have a lot of work to do to improve these materials. This is a promising step toward the future of tissue regeneration and repair."



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